• No results found

Genetics of chronic subclinical mastitis in Norwegian Red cows

N/A
N/A
Protected

Academic year: 2022

Share "Genetics of chronic subclinical mastitis in Norwegian Red cows"

Copied!
162
0
0

Laster.... (Se fulltekst nå)

Fulltekst

(1)

Philosophiae Doctor (PhD) Thesis 2020:19

Genetics of chronic subclinical mastitis in Norwegian Red

cows

Genetisk bakgrunn for kronisk subklinisk mastitt hos Norsk Rødt Fe

Philosophiae Doctor (PhD), Thesis 2020:19Elena Kirsanova

Norwegian University of Life Sciences Faculty of Veterinary Medicine

Department of Preclinical Sciences and Pathology

(2)
(3)

$,$1("0-%"'/-,("02!"*(,(" *+ 01(1(0(,-/4$&( ,$#

"-40

$,$1(0)! )&/2,,%-/)/-,(0)02!)*(,(0)+ 01(11'-0-/0)6#1$

'(*-0-.'( $-"1-/''$0(0

*$, (/0 ,-3

-/4$&( ,,(3$/0(15-%(%$"($,"$0 "2*15-%$1$/(, /5$#("(,$

$. /1+$,1-%/$"*(,(" *"($,"$0 ,# 1'-*-&5

# +012$,

'$0(0,2+!$/

(4)

(5)

##"

&#

"$!'

!""!

!%#"

"# !"

#!$#

%'.+4271(

!,)&4))(-1+342+4%0*24249)+-%1)(

%56-6-5-1(%-4;'%66/)

20%6-'')//'2716%5-1(-'%6242*0%56-6-5 )/)'6-21%+%-156,-+, 20%6-')//2716

0071)5;56)0

'6-8-6;2*+)1)5

#"#$'

"$!'# !"

#!"#"

1-0%/5%1((%6%

6%6-56-'%/%1()1)6-'1%/;5)5

)120)9-()552'-%6-21 67(;

1%/;5)52*+)1)):34)55-21

(6)

'!"$#"!"$""

$""

! "#"!$#$!"#$"

!!"

!"%

(7)

!"#$$$#$%

# &'$$ !$$ ( $ % &$

)$*$%$$+,)-##$,).

/ ("%0"$#%(122334(

/!&"#!%"*$/&$#.,5&6$& '

%"&"$.$"$&"!"(7"!./"##$

!#%$ !$&60*$##!####&"

!8#$$#$8#&%! $!# 9""#"#

$,).###.*$$$$$"$(7$##%.!%#

&!%!$#%(

#.1:1:

#$*

(8)

) 0;

$"#$$#!$$$"$#!!$$#%$!$#!$##"

+- * 1:: ::: ##<!# #& $ $!. " % $#

$$(*#"*"$"#$$#!$$+-$"$$%

"#%$&&$$$$.$#$$#%"$

=$( . &$ !$! $ $ $ $## !$

$$$($"$$&$0+0-"#$.

$!$&$$%"#%$&$#&$#$"$&$&$!$#(

7$#%+8/-.*$##%0$#$>2"

$!&$!*#$$$#$*&

!$##+-($$$%>$%

$*#!?::::@:::::##<!#+?:.'>::.

'>?:.'1::.'1?:.'2::.'2?:.'@::-A$%$*1:::::

@:::::##<!#.$*#%+1::B2.@::B2-( #"!%

$ $ ?:C> +?:- @::C> +@::- #%( $!

$$#$%$*$!:(:>:(>:$$#$%:(2(

6$&&$#$$!#$*$.&$&!:(3

>(

$!&$!!8/"$"$&!'$$$

"%+ -&$&%!23D?0"##+8//-(#%

$&#"#$#%!$!+8-!0"##!

$"&+C2?@23E@-( 2E$&$$8$$

!#$*$(,**$#&$##%$!$

+ -&$$$&$$8.>4>&$$$#%%/&"$%

(9)

8% #%$ +/8 - $ &$ $*#* $# % (

*#$&$$%"$*$&#$*$

$$$. $ $##" !#=$% $ ( &"

!$+'F'!$-#$&&+#####-"

$ 1::B2. $ $$ 7 '&. 8'> $$

""$+ -.#"$&$$&$>?:.'1::.'1?:.

'2::.'2?:.'@::@::(

7". =$ $# # $ & $$$ $ $$ $

$$.#%$!#"$!"#$##!"#

##+8,-!%0A$$&$#$!

&!$ $& *#" +,G- +8 ///-( 0* $$'9"$$*

#%!$$+0'980-$#0 *#$0 ( $&$$#% $& =$ #*# # & " $ "$!"#

8,!#!&"$$&,G!&"

$#,G(6$&=$#&!%$"!$

$!!".##$&!"$###$*$&&"(

/8/G.&"0$$&+CE-#+CE-,G

"$( & $# ! # !# ##&-1 8-642 $ 64)362'2''75%+%/%'6-%)$>1>:(##&$$#$*#

?D2EE@@2$$##%=+-&$&"$$>:2>1.

$*#%. *" "##& #( "# * $ 8 /G. $$

$*#*!"$#$$&$!$#"$&$#!!$$"(".

*"'&"#$;25-1+$-$>:2$!&!

$#,G.$!#%$"$#!$&$$$$".$

!%"$&$!$#(

(10)

/"!!%.""%*$""$&$#&$#!$!

"#%$&*#!$$0#($#$*$

&$##%$!$"#%"$&$*#"$0

$!$$$!*$&"(*.

* ##"# =$ $# & $*#* $ "$# $#"= $$

&"#$"$#!*!$!$#&$#!$!$

$$$0"!!$##$!$#(

(11)

0 0

$"#$$!$$*#$&*$!"#!5%####$!#+*

1:: ::: ##<!#- $ #& $. H * $$( 7#

#%"#$$!$+-&"#$*$$*&H$

&$&"($$&"H"$

#$*$$*&#$#%("!&$

!$!!%$!&#"##(/"$*$

" H $ $ 05 7 +07- "# ! !H# ! H $$$

&"#&&$#&$!$$#5%####$!#(

/$#/.#####+-07%$#>$#2"$#H$!

&$ ! >1 % & & &!$ #####

+-($$I&#$!>*$$!#&H*

5%&$#*$?::::$#@:::::##<!#+?:.'>::.'>?:.'1::.'1?:.

'2::.'2?:.'@::-A&*$&H**1:::::&@:::::##<!#.

#*$ +1::B2A @::B2-( / $##&& # ## & 5 ?: +?:- ##

@:: +@::- H 5 && #%( $! *&

&*$:.:>$#:.>:&*:.2:(65%&$#.

!*$:.3$#>.#$!!##!>1#$*&(

$! &$ ! # *$ " $ $# // $ $"$

+ -!&%$!*##%!$+8-07+C23D?-

& % 5 $# +C2?@2 3E@-( G #% # 2E 8J!5$$$!$&$$$!###*#$*

&( , H * #&$ !H + - ! $&$$ 8 $

&!.#>4>&$$$&#%!/&"$%8% #%$+/8 -

(12)

H $ $*#* $#&$ & &$ *( 7# H*$ #$ &

##!##!#$*&$##"!#$$#$(

&" * !$ +'F' !$*- #$& & +# # # #

#- # $$$ 1::B2 $ $##&& $# 7 '&. 8'>

$"+ -( &#&H"!*!$&$$

&>?:.'1::.'1?:.'2::.'2?:.'@::&@::(

)% * # $& $$$ $ $# ! $

&#*$"$"$!"#$!"#I###+8,-$

07%!5%&!$*#*$+,G-&$%!#*,G +$# ///-( 0* $'*$$* #%! +0'980- #

%H0 $#"$!"#8,5*&##$&"%#H*$(

$&$$ 5% * &# # H*$ $ 5* % ! 5% ,G

!!#$&!&"!#*,G(65%*#*I!H H#!!$&!$!!"*H$###

#5%$#&"#%H&$$*&$"(

/$#/G#&"*07%!5%+CE-###*+CE-,G"(

&## $# #5* # $ "#" +-1 8-642- $$ ! 64)362'2''75

%+%/%'6-%)!!>1##>:2$$##&&$#"$!"###5*(#"

# ?D2E & E@@2 & ! $&$$ ##$& "% $ &" $$ !

#*$ >:2 & >1 !!#$& ! "$!"# ##5*( 0"# $

$# /G $$ 5%$# &"#% $*#* $ 5 $ !# *

$#!! $ "( 7 !# '&"#$& *;25-1 +$- & $ >:2

$$!&%!#*,G%5$#5!$&*5%$#

&"#%$#$$**&!$$#5%$!#(

(13)

"!! *#$& $ $# H# * $#&$

!$!!#$&&$#&""*$#$&*$07(%#$*

$ & &$ ##$& & ! " *

&$&**#*$07$&(%&*$#!"$!

! $! ! *# "#( / $##&& $$ *

##"#I $# * & $*#* $ !$& * 5%$# &"#%

&"#$&*5%$#*$&!H!*$$&#*$#&$!$!

$$07&##*!$##$!#(

(14)

,,0G/ /

*$%$*&

, 25!%7475%762520)

!#!%=%$"#$ $

#$$#$$

%##

$$#=$

"#=%$"#$ $

; "&;$#*$$

,G $!,$&G#"

70 7#$*%0

,G !$$!,$&G#"

!$#$

!'$ $$"%

/ /#"$

/8 /&"$%8% #%$

$&$9"$#$$"!

#0 #&$&0$"#$ $

$!!$##

!$0 !$0$"#$ $

!0 !&0$"#$ $

60 &$$%60$&%!

0 &$0

8, 8$#,#"###

(15)

K K"$$*$$

0 $!#0$"#$ $

0'980 0#$!9"$$*8#%!$0$

!$##"

"#$$#$$

!$##

*$$

8 $&#"#$8#%!$!

#&$##%$!$

0 0$"#$ $

(16)

#$$$#"##!*$&!*$$+25!%7475A L<<($(#!($(&*<-

!J%#' $1

! J%#' $@

!J 8%7>""$

J!#!E J%#$,>

J%#$'$3

#%/52.1291%5J!$+'F'!$-#$&>

#J!$+'F'!$-#$&1

#J!$+'F'!$-#$&2

#J!$+'F'!$-#$&?

#%/52.1291%5J'F'!$!$#$&4 J"%$#$$$$$1,""$

J7'&. 8'>$$""$

J&#%#%'2'%&

J/!$#%M$$&1

J!$+'F'!$-#$&>+!#!&$!"#$&$*$%#- J!&$##&"""

$J!%$/7

J$%#&$$$!$@

J#$$>

J$%##%#$!

J$#!#!

J$!#$>1

(17)

J"$%&!#=#*$""$

J0 2#$&""$

J#"$!$#%>4!! 1

!! J$&#"$*$$@

!J!$&&2

(18)

/78 80

(6,7

29,74(90;,":)*2040*(2(890908#7(098-57,4,90*;(2:(905404(07>(992, ($*.,(6$&. ('./(#(

2741%/2*%-4; '-)1').1:>DA $L>:(2>E4<(1:>4'>E>:@

(6,7

+,490-0*(90545-(4+0+(9,,4,8--,*904./7540*":)*2040*(2(8909080457<,.0(4

!,+*(992,53)0404.,453,&0+,885*0(9054"9:+>#56525.0*(22>885*0(9,+

53(048(4+ (9/<(>470*/3,494(2>808

($*.,(6$&. ('./(#(

1-0%/)1)6-'51:1:A $L>:(>>>><&(>144E

(6,7

=67,880544(2>80854(4+0+(9,,4,8-57/7540*":)*2040*(2(8909080457<,.0(4

!,+

($*.8(,%.((N.,(6$&. ('./(#

7&0-66)(622741%/2*%-4; '-)1')%17%4;

(19)

(6,7%

#7(48*7069054(2 75-0204.5-545*>9,,70;,+(*756/(.,84-,*9,+ <09/#<5

"97(0485-!,;,(28(4+0+(9, (9/<(>8--,*904.":)*2040*(2 (89090804(992,

('.($*.(#.(#&.,(6$&.(OH.8(

,%./(#(

4216-)45-1)1)6-'51:>D.$L>:(224D<&(1:>D(::E4D

(20)

/0)/

(*1.75:4+

$"#$$#!$$+-$$%#$$#%$!$##"+-

*1:::::##<!#$!$##&$$!+)+6!>DD@A

#(>DD3A8#(1::D-(6$&"#$"!$#"$9"#%

!$#+6&!'$##(1::D-(8*$"#%.#$$#!$$+-

*"$$&$0+0-#$#%K"$$*$#$+K-.

"$&"#%$&!$!+#"&##(1::>A##(

1:>>A##(1:>E-(*#.#$$

$#%$$%$"$(6."$&&$

"$# &" $ $ $$% $#&$# "#%$&

$ $ $% # " $ $ $ % "$& $$(

&$ $% 6 0$& %! +60- *$ !$# !

"$.$#$%*$%!$(8%$

*"$#%##$!%$>D34(

#&*$###%$#$$$#&""&

!"(,%"$&60$!$$$&%$&

$!$0"#$.*#$$$$"&#%#%$

"$"$$#$!$$!*&$*#"$"

#$0$"$##$"#$(

(21)

#/,)7,,+04.675.7(3-5757<,.0(4!,+

,$& / $$$$#*#!$&&!

0"#$+(&(-($#"$$&&#0$

>D34+6$&#(>DDD-($#!$#"$&$*#"$"

#$1:>@#$*&!$##+-($$$$*!%

#&!!$##+A"#(>DD1-(!$

#$+A"$#(1::>A#-$"$&0($$#%"

$!%$%#$&!+&PQ1::D-($#$!$

&!$ $! $& *#" +,G-( #"# ,G $ 0 $&#

&!$ #$ "$ $$ +,)8- !# $ " % .

$&+-$&#"#$#%!$!+8-+-#$$!$

$ ". % "$& !$ !$= +G0 1::4A(&(-(

0#$$$!8.###&!$#$$!$=$

#$M$&!$$*$"#+#(1:>>-(

$$##%$!!$=$=$&!

$$*$"#*$!!(!$$&&$*$&"%#$$

$$*$"#(#!$$=0$##$&$&"$

#$* $& &$* & $ $ +(&$(!-L 8"$

+12(?@-."$!$+11(?E-."#+>?(EE-."&$#$%+>2(43-.+3(>E-.

# # +@(:1-. #& $!$ +1(>4-. #*$& +?(@:-. $##$ +:(??-.

!$#$&+2(3E-.#&+:(?2-.$$+:(2?-!!+:(@1-(

"#$=0$+E4R-+21R-(/!$

$ "& #% #%$ % !$# !#. $# $

*$%!60(

(22)

(89090804+(07>*(992,

$$$!9"#%$$$%#.$M%

$+6!>DD@-($$$#!!$"$#$$#

%!!."!#!$###$&$$"($#$$

*$$#&."!$#"$.$$

$!$#$(*#!$$&""$#!!$)+

6%3,;/2'2''75%74)75 64)362'2''75%+%/%'6-%)#$!+!$1:>@-(/%.

%74)75$!!!$"$&*$!$$.$# %+%/%'6-%)$!&

#$&"$*$"#$$#*$!$$(,$"$

*$!+S#(1::1AN5&#(1:>E-!$#$&.$#

$## !$ $#. % !% $#% $* " $" #$$& !$#'

##$&"$+7$&">AG$&"$#(1::DA,&$#(1:>>-(8"$

*#*$"#"##$&!$#'$&##(,%$#$*$

#"%$"$&#$$##"%!*!#$"

9"#%$#$$(6*.$$*$&$

!##% !*. % $" " #*# ( / ! .

$$$#""!#"$$$$!$#%$"

!%%#$*#%$$!$#($$!!"

$$*."!#"%&$!&$#$###

$$!!!%&#$#$!$#+$###(>DD>A M#(1:>>-(

(23)

0.:7,$$$$(!$%$#&$#"""9"$$%

#$($&$"$*$&&*"9"

#*#""&#."$&!&$#$####$&%

#*#"(&&$M%$!!"##$&&$*$$$!!"

.$$!$##"!%#$#!!$(

"53(90**,22*5:49(804+0*(9575-3(890908

$*$!$#$$$$#!!%$"9"(

$#% % *$& !#$$. " # # $ !$# . $ $ "( $ $ ! $$"#. $ #$$#

(24)

%!!(K"$$$"!$!$#$"!$

$$$!$$&(8*$"#%$

$#%9"!$##$!#%$!!"##."#%!%

!&+$%#(1::E-$*$$!T?::::J1:::::##<!#+

#( >DD3A 8 #( 1::D-( $# $ $#!!$ $## $ +$%#(1::E-$=*1:::::##<!#+#(>DD3-(

6*. *# " * #% $ # #*# #"

#$*#%$$*$$!$!%$!*&$*#"$

#$"#+(&(6#(1::4A$$&#(1:>:A#(1:>1A ,#(1:>4-(7"!.*$&$$#$%!+0"

,$. 1::2-( $##%. $ $$ % !$$ J #$$#

"#$$#+$#(1:>4-("$#%##"$$

!$$$*$$&&!$!%"$(/&$*#"$$$!!

"#&!#$'*&!$##+"#(>DD1-(

",2,*9054(.(0489/0./"53(90*,225:49

#$ &$ $& $ !$# $ #$ &$ $#!!$ "$#

$$!$#+0$#(1:>4-(#$#$

$"&$##%$!*"#(6*.$!$#"

$!$,G$#%!&$!#&!+1:>>-(

, "#$ $$ 8 ! $ $

$!(8$$K$$#%$#$&$9"$#$$"!+-$

$(!$'!$$###+*$!&$*&-

$#$$&$*"#$("+#$$#"#-$$=$$&<&$

!!!(!#$$

(25)

$!$#$""#$(!'$$$"%

+ -$!9"#%"!$$%!$$$

%+#*$P0$>DD?-($$!$##$"!$

#$##"$&$#&$#!$!!#=$."

"$#$J$#$%.+)+Q#(1::2A#(1:>:A##(

1:>>-+)+#(1:>2A"#(1:>?A##(1:>E-(/

$0$&$$K*$"#%*$!!+, J25!%7475

"[email protected].>@.1:13+#"&##(1::>A$##(1::DA##(

1:>>A##(1:>E-($#K$&*, 4., >1.

, >D, 1E+#"&##(1::>A##(1:>>-0.$

, ?., E., >2., >E., >D, 1:+#(1:>@-

"$0#( "#"#%"$&#&$##%$

!$+ -&$$$%$&+&#(1:>4AU $*$%

& #!$#-(7"!.$&"$%%' #%$ $ " $#&$# "$ $ !#= $. "

!$$$$%#+'#(1:>1A##(1:>E-(/$*

$#&$#$"$!!"%!$$*$"#*&$M

$*$&&(

33:4,8>89,3

$!!" %! % ! $$" & $& &$! $

#$$$$$*$!!"%!(/$!!".###

$$.$$%&*$$&#%$*$*$!!"

.#9"$+##"$PM$&1::>-($&#%$.

$.%##"$&=#$!"#"*$$&$$$!!"

(26)

##($#$$$!!"##!%!&(

$&$*".!%!$&!#$"

$$$!&!&%$(#$$

%74)75"*$*$$!!!#$##!!&&!

+,%##(>DD4-($!%#$$#!!$%$"$&#$*$*$

!& +7$&" 1A 8! 1:>?-( !##%. $ !&.

#>##%$*$'$#!!%"&$&!!

+/7'γ-.%$$/7'γ!&(%$#

$*$!&!"&$&##$*@:#$&.

%$ " !! # > ##. $ $V @:.

!&(7".!$$$&#!$&!@:/7'γ

#&$&=$$$*!&(#%!&$

%$"#>##!$&'$$$*

$$$&!$*$&&.!$!*$&"%!&

#% $" % $* !&( 6*. !& !% " #&

!"$#!!%%$$$&.$"$##%

#&$# $#!!% . %$#!!$ *"##% #&$# $"

!&+6!$M#(1:>3-( #$*$*$!&$$M

$$'$#!!%!%$$$'$#!!%%$+8!1:>?-(

*#$#%#$*$*$!&+ *$#(1:>2-(

$%"&'#1%$$#"$@>2+/'@A/'>2-"#$&

$ $" $ !&( / %. !& ! $*

$!!" $!"#$ % $#"$ >: +/'>:-( # $# #$*

$*$$$"%$!!"!#=&$##'#$(

(27)

0.:7, #$##%#$*#%$*!&(/"9"#*#"

!&!$&'$$$*%$&#!@:$&!!

+/7&-("###$##%$*!&"$#"$@

>2+/'@./'>2-$*!&( #$*#%$*!&

"/'>:$$$'$#!!%%$$&##$&(

*90;09>5-.,4,8

# &! $#&% $ ' . $& $ #$$

(28)

#$!!0 $+#(1::4-(%0

!0 .0 +0 -$!#0 +0 -(7"$!0 $%

$!$! $!#$$%$(0 #&$

!0 $!$$(#0 $$$!$$

$$!$$$$(0 !$$$!

$! +"#$-( / $$. *# % 0 . " !$0 +!$0 -#&$&0 +#0 -=$($&"*&"#%

"$(!$0 $$#$!0 %$$$$%$

+W,$#(1:>4-(#0 &"#=$&$'-5+$&"$&&- 64%15 +$ &- % $$& $ "#$ $ !"#$& $

"$+,#(1:>@-($$$$$&0 #%!$

!"!&9"+$1:::-( !$&$

$##$$$$$&(8!&"#&

=$&$&"#%&$.".$*$$

&.$#J$*$$(!##%.&=$$##

%$#."'&$$(($&$.$#"=$

&$&$!($&$$$%$$$"%&

$9" ("$&$!$$$&""!$

"#$&$$$#$*$$+P$&#1::@-( !%#$

$ !$$$ =!# !$! " "$# & $

&! $" & $ "#$ 9"( !%#$ $

!%# &" !#"# # $ $$

$$&($#$!$$$!%$#"## '."

$$ !$ !$ + #( 1:>E-( !$ # $

"#"$#"!#=$ !!!(/!$.#&

(29)

!#"#!&$!.*$ !&$"

&"#$ #$$&=$+##(1:>:-( +7$&"2A

$=#(1:>1-$&!$&$$%!9"#'$$

9"$$ &$!9""$&$( &$

$ % #% !$ !$. % "$& " ! $ ##$&

9"$&( # $ !$ !$ $ $! # $ &

=$&"#$(

0.:7, #&$##% $ !$ + -( !$ "" !!

$%$$ &$($* #=""$

&$$$*&.""%!&$$$$*&(

(30)

+7$&" 2- ! "! $#&% $&#% * !$ $ #'

$$&!$+$&#(1:>4-( #"$&#$$+8#(

1:>@-%*$##%$+$=#(

1:>1-("$#$%$!"$#&"#$&!! ""#

$$$$"#%$&&&"#$!$!$$(*.

$!$ $!*$&*$!"$&

$$#%$!$&$$8$$$+&#(1:>4-(/

*$&!$ &$*$9"%

*$##+!1:>D-."%*$#%*$"#%%"$&

#$*#+&#(1:>4-( $*$##!*#"!.!$.&

!9"##%""##%**$&!(7"!.

!$&$$K$$*$$$=$$$&###

&"#$$! &!=(

$$##%.$&#(+1:>4-$! $&#%*&$

&! $ &"#% "$ # &$ &! "$& *#"$(

. &$!%"#$*&$"$*&"#%

*$$*$&!(

(31)

/76);

$!%$!$$"$&&$"$#

&"$$0$%(6.##$&"'$!!"#L

>( $#$*$$*$##$!$$!

$$#$%&$#$$

1( 8! $$%$&$$$.

#$*$$

2( "%=$$#$&$&"$!#$$&#

,G

@( #%=$$#+!0 -$.$-18-642$ %+%/%'6-%).

&"$&$#

(32)

) 0;768 80

%3)4

29,74(90;,":)*2040*(2(890908#7(098-57,4,90*;(2:(905404(07>(992,

$$0#%>1$.$#

?:'.>::'.>?:'.1::'.1?:'.2::'.2?:'@::=>:::##<!#+?:J@::-(,$%

$9"#>$#"$*%$$1!

*$=#.$:(*.$!$#$%

$$2!$*1::'@::=>:::##<!#.$*#%.#%$

$$% #& #$& "#$$# $$( "! % $ $

?:C>+?:-@::C>+@::-#%$!$"(

! 60 $ " +C3:> @@:- $!$ *$

! % #$ $!# $#$% !#( !## " $!

&$#$+C1@2??E-(#!9"%$&!>(1R +@::B2-?>(4R+?:-(!"!%>:@?:>>3

@::(!@(@.9"$*#=$!#%41:::$!$#(

$!$$#$%#*$&!:(:>+@::B2-:(>:

+>::-($!&$#$$&!:(3+?:

@::->+2?:@::-( $$##%.$$#$%

$!:(2&$#$$&!:(D +$?:->+$?:-($!&$#$!$#%$#$

&!:(:3+-:(2:+@::-(,"#$$!$&*$

$$#$!$$$!*$&"#(

(33)

%3)4

+,490-0*(90545-(4+0+(9,,4,8--,*904./7540*":)*2040*(2(8909080457<,.0(4

!,+ *(992, 53)0404. ,453, &0+, 885*0(9054 "9:+> #56525.0*(22> 885*0(9,+

53(048(4+ (9/<(>470*/3,494(2>808

>1$$!8/."#%"$& $

$$%$&$&$(%!0"##+C23D?-

!$$%$!$!$"&+C2?@23E@-(7$."&%$#

*$$+;-&%0$#"#"$&%!

$&$&$#+C@>1@E34-(#%.;!$$8 +CE>2 D:4- &% ! $ $& &!$ #$$ !$=.

8*$% (&!$#$$$$$&$$8 +C2E"$9"8-"*$ &$##$&#$

$#$&(#$&+"$9"&/C>4>-#%%' /8 $&$M$*#*$#%(

$$!$#$&$$&$$X?::::

X>:::::##<!#$%$+?:>::-.$(($#!#

!+-%#$,>+-(*.$$X1?::::A 2:::::A2?::::A@:::::##<!#%$@::$#%$!$#

$&$$&A%#' $1@+!A! -(7$>?:.

1::1::B2.&"!$+'F'!$-#$&&7'

&. 8'> $$ ""$+ - & $$$( "#

$##"!#=$%$(7""$#"$%$

#$%"##&$*#!$$0(

(34)

%3)4

=67,880544(2>8085-(4+0+(9,,4,8-57/7540*":)*2040*(2(8909080457<,.0(4

!,+

*#$&#$*#%$$$!8//

#!0 =$$#!"$!"#$##!"#

##+8,-$$&"$!#(,#!#!%0

#$,G(0 =$"$$$$$

#"%"$!#()$&0'980#%!%!$$

& =$ " $!# &" % $&<# ,G

#%<##$&(&#$&=$&

#=$$&"$$&,G("$&%#$&*#

$&$$$&=$7&$#%#$+J!#*$&-

!#+*'$&!#*$&-($&$$$"$

#"%"!&&"!#.$$$&$$$&=$

"#$#%"%#*"!##$8,!#($$$

&$""%$$#$&$$

0(

%3)4"

#7(48*7069054(2 75-0204.5-545*>9,,70;,+(*756/(.,84-,*9,+ <09/#<5

"97(0485-!,;,(28(4+0+(9, (9/<(>8--,*904.":)*2040*(2 (89090804(992,

(35)

7"$&"$&"#$$#!$$&=$$#

$*$!%$*!&+-!#!#"$(

$# ! #* 0 $!"#-1 8-642 $ 64)362'2''75

%+%/%'6-%)$>1>:2($$*$"##$,G (####&$$#E()##&#

$#"( 7". !0 $# ! 9" "#

$*$&$$##%=+-&%#%($"#$

?D2EE@@2&&"$$>:2>1$*#%*"

"##&#(/&"$%%#%$+/8 -"'&"#&

$&$$$!%>%1###$*$$!#$!"#

$>1($#$&$$$!&"#%$$$$$$

!&"'&"#&$!#$!"#$>:2(&$

" $&$$#% $& = $ &" # ,G

##&%>:2!$&,G($# &#

= $ ##& % >1 $ &" # ,G (

$&$$#%&$$$#$&,G$#

!#(/$$!#&"%$&#$!$#&$*

&!$!!"!"$&##$($=.&

$$$$!###&%>:2.>1#.$*#%($"%

&'$" &"#$ % & $* $ "$& $!!"

&$!$$"$& 64)362'2''75%+%/%'6-%)$0(

(36)

0/ 6

403(28(4++(9(

/8///.*$##!60+/#.%-!>D3D1:>E #%( " $ $ #. $

$%*6$&+1::E-$@:::::##<!#$&#

#*#$*$!$###"!"!$+"!!$$$#

6%&$$$*D1<@E.>DD1-($$$%+>:-

>$%$$$1!$*#

!?::::@:::::##<!#+?:.'>::.'>?:.'1::.'1?:.'2::.'2?:.'@::-A$

% $ $$ 2 ! $ * 1:: ::: @:: ::: ##<!#

+1::B2.@::B2-(%$$8/$&"$&1%

#&$$##$$$$#&'!$$.!#&'#$&

&$"$&2%#&$(*.$L?:

@::$"!%!#*$&$$#

*?:@::=>:::##<!#.$*#%."$&1%$$1!$(

$"&$*$!$#&%$"%$$

$!$#(%$%#&$#*$#$%

$ $$ $ ! 0 ( 7$##%. . $

"#%"$"$&$*#"$"#0.#%(

$%"$&$2#$%$!$#

!1>2:?+*$"##%$&#*$&-#%!'%$

# >? 0 $#"( + ,- ! 60 "L

%<!$#*$&L -!1::E(:>1:>E(>1,L!1:>@(:>1:>E(>1A&

#*$&$!%#$"!L!>DE2!"$&>J2#$

(37)

,A$*#!#*$&$##%L!1:>?:%A

%L ->@4E:,->2@?:( $#"$&3:>@@:$$&

>1:D>14>@32423$$*$"#$$&$#."$!$

*$!(!"+1:>1-""$#$&

$#%$#"$&*$###$$$!$/'"!$!#(

" .!##,.$#"$&1@2??E$2?31:2*$

$&$&$#D22:@D$$*$"#."$!$&$

#$(/%" $!$! "

!"$##$!$$(

/8//.&%$!$!23D?0"##$E>2D:48!$$

% ! $ 2 ?@2 3E@ "& +$ #*$& $ >D3D J 1:>E- $

$& 3 2:: 4@3 *$ % . " $ $ $ 8/@>1EE34$$*$"#$$&$#(%0$*$%

+(&$(!-.$&&$M$0.#%(

%0$"$& %!$=1?8%+ %!$=.#- /##"!$ ,*$8?: ,$ +?@A /##"!$ /(. $&. A ""!##$ #(

1::D- !$ $ /##"!$ ,*$6 %$& ,$ +333A /##"!$.

$&-(7". $!"!$$&8(

/8///.1:0$ $!#8"$=$!#.

&$)$*$%$$.###$#!#

=$$&(#$"!

#*$&.$$$!=$!$M$&$$,G#

* >::. $ $& $ +T >::- # $ +X >::- & $& $ !$# "$&

#$(/8/G.#*0!$$%#

,G.!=$!$M$&$&"(

(38)

"9(90890*(2(4+,4,90*4(2>8,8

/8/. *$D(@+ /(/(.%.A((!-"

$(+-*$!#*$$$

$!$)) /&!+N1:>2-"$&#$

$!#$#$%!#($!#$#$%!#$"$!$

."$$#$"!+#(1:>1-(7$!$

$$#$%$&#$$#$%!#"$.$!$

&$#$$*$$#$%!#"($$

$%."##$!#$##9"%$"$"#$

+$#>D41-(.#9"%!%"#$"$!$$#$%$(

/8/.$$#$%&$#$#"#($!$$#$%

$! &$ *$ $*$ % "! $! '%. !

*$!#.&$$"#*$(*$$$*$

% &!$ ! *$$ +- $ #"# &$

#$( 7$##%. +- #"# % )

%!$(

*$!$!$8/"$8//.$"$!$

$&*#"+,G-%)?"$)+N 1:>2-(#"$$=!"#"#$"&

%$#*$$+;AG0P$&&>DD>-0$.;$&*&

"&%$='&$!(;"

$" $ ( /$$ $&$$ 8 " #% % "$& *

*$ &! $( &$ *

$##%$+$=#(1:>1A0#(1:>@A0"#(1:>?-##

(39)

#"$&#$$+8#(1:>@-(& ""##%*

*$&!&D1(EJD2(1R4E(:J4E(4R!"!!"

$*#%(.#$$$$&#%"$&

/8 +(9$&$$!$(!-.!"%#%$

. $!% $& "! !"$# $"%( /8 $$ "

"!$".$$$$$$&

"#$#$$$#(

/8///.$$##%=$"#$$$$&

! "$& 8 8$! *$ 4(>(> +8 . N##

#$$ ) .(&(!-( $! $ $ & =$ #*#

&"$$&#,G.!"#$#'$##$&

7#$*%0+70-$$!'*#""($&$$

#*#$?R708'*#"+K'*#"-(

$!$$##%$&$$$$$#!

!# $ 8 /G. & 91 *(>(@(? +* #( 1:>@- &0 *(2(1:(D +0$P#1:>:-$0*(2(@(>+L<<(0'(&-"(

&$$&$$70T?R$&0,!$$

6&'*#"T?R$91(/8///G."$&/8 #%

&"$.7$='?R#*#,!$$6&'*#"

≤?R.$*#%"$$&$$#*#$&=$(

,$ $ " # !$#%'$ $& !"#$#

% +G$ #( 1:>D-( ,$ $ $ *% *$* $&

#$ ! ! $& $ $& $% ! +6 #(

1::D-(/#K.$$%$&,$$$##"#$$&

"!#&$*(/8//.$&$$#*#$$$8

(40)

$&$$#"!8$$"#%?R!!'

$$&$$#+#(1:>:-$!#!(

,453,<0+,885*0(9054"9:+>

/8//. "#%$$$$$8/

8$$%$*#*&<!!#&$(! #%

& ,*(>(4':+ "##(1::3-$0*(2(@(>+L<<(' (&<-"( $!!#%"$$%&$$%

$(/8//.;"%$ !#$0 0'

!!"$.*$!''!""$$!$

8!#$&$"'""."#$*+*$*#(1:>1-(

"$& $ $"# 0 0'!! $!. "$&

#%&$ "$( #%&$ "$ &$* $* *$ !$=

$!$"##%$%"$&$$!$=#(/8//.

$$#$$!$=$!!8&%*$% (

*$$$!&$$$$$!!"0 0'

!!"$+*$*#(1:>1-("$&$$#%$0 0'

!!*$!.$&$*$!$$$"$

$!8(7".$$!8

$$*#"$*$%0 0'!!&!$$#$(

4(2>8,85-.,4,,=67,88054

!#%$&=$*$$9"$$*#%!$

$+0'980-!0 9"$&"(!"$

9"$$$$$&$!!0 9"(/"0'

(41)

980!$$%=$#*##$&$

+8///-(

0'980!$$*$$($$*$$+0- M%!*$"!#!% + -!

0 ("$&.!#$$$. $!#$$"&%#

"$#%!$M$"$&$9"&%$$$!(

$$##%.%##"$!$9"$%#*#"#

+ -( $# . 9"$$$. $#" #$* 9"$$$ %

$$&"!!#$$$%##"$&#'

#(%##+-*#"$#"#%#"!$

!#$$$"*$#"#(*#"$##*#

&0 $#%!#.$(($&*#".##*#&0 ( /8///.@:%#"$980"$&F80;,00980

"!$=.$!$=0F+/*$&-%$#$## !$

#" $&#. ## % !#$& "* #%( F80 ;,0 0 980 "!$= $ +L<<(!$(!<- *$ $& $$*$%. $$$%

"$$#$% % "$& $& $&#. # 80 $$$$ "

!$$$980!$&$#;,0/(6*.;,0

$$$$&9".$$$## $#"$&"

!#$(6.$$#!#$&"*#%$0'980"$%

""$%(/$$.80"$&$!#%

$M&&#9""!#$"(

*.!#0#$#"!$$0

!#$&!$ ($"0$"!#"##%$0

(42)

80$$##(7$!$&$*#$

!#+!##-$#"!$$$!$=(

/8///0'980!"*#"=$&#$#

$ $ $ "#$$# !$$ $ 0 .

#%( ##&$$$!$&"$&8$!, #+;#(1:>1-

#%!$!$#$0&!"$$$$%(

9"$%#*#&=$!#$M$&*#"&$=$

+"$&- &. $ ! #*# =$ $ ## =$!#

$"$. !( / $$. =!$ $ $ $ =$

#%&"%$$##"#=$%$"!

!%. $$ ## $ 8,. # %!% !(

$=$!%!##$$%$%'$$$$"

$$$&$%#"%##$8,!#(

*$&0$!$$9Y2(1+L<<(9#"(!-

"+8///-$$%!#&=$*$8,

!#( $ $ $#" $! $= "$& & +..!.

.. -$&"$!#(

*#0 !#$#!8,+$&&"$&#

,G-##$=&!#"#$

&(*&=$$#$%*#"+-#"#

#!&$=&#:(2(6.

&$!#&#"#&!$!

!#$M$ =$ #*# &( #"# & $

=$ #*# & $ 1 ! "( $ ! !

$ & =$ &$ & $ ! ". $((

(43)

ΔC+&&-J+&-( $$##%.$$%##$!$

%!#$#"$$(!#!$$&,G

!#,G"("!!#"#&9""#"#

"$&#$$%#$""%+8///-$$%##$!$

>::R+±>:-(

#$*#%.0 9"$&$$#=$#%$!(/8 /G!0 $#!##&-18-642%!$$"$& %+%/%'6-%)$

>1>:29"$#%&!&$&"(

!# $ = $ > " $$ >R

$$##$<!%$"#"$"&=##"#$

$"#$####$$"#"(#"#"$"$

#$$(,%9"$&0 $#!!#.##$*#*&$

*$&!!%$$$(*.9"#%$

$$%8%!$&!*#$$*$"#($!.##*$##$&.

"$$%8*$!0 9"$&+8$##(1:>2A##(

1:>?-(,"$$!"#$!%&$*&#%!"#!

"$$$$&!$*$($%#%$$#!#

!%*#$$##%=&+'#(1:>2-(,"%"$&

!$%#%$#%&$%$$$.$#9"$&$

$& $!$ *# " & #$ *$

=$#%!#(

(44)

;0) 0 /)/

$! $ $ "$& &$ "$#

&"$$0$%(%$$$#$

!$#*$&*$!&9"$$*$!!"$&

$*$& &( #$#% * $#$% $ $$.

$#"$&*#!$.!%$$&$!$#

#&$$!(*.$$*$"#$$&#,G

=*$&=$$#$8,($$#&$#%

!$%$(

>1 #$* $ $ #% $ $*$& $

#$!$#(*#$$.$$$$###$#

$$!#"$$(&&$#$$!

!&$.&$&!:(3+?:@::->+2?:@::-

$$8/($!$$#$%#&!:(:>+@::B2

@::-:(>1+>::-!&$$($!$#$*$

$%#"#$+)+#(1:>:A,#(1:>4A%#(1:>4A ,#(1:>D-(*#"*"$#$*$+*$%$

#(1:>4-.$$$%!$!$*$"#(6*.$!

&$!."$$#$%&$#$$$

! $#%. " " $ !# $!$ !

$$$$$($!&$#$#$*#%$

$ *$"#% *% ! $$* #$ :(DD *"#

&$*#$':(4?.$&$$$$+6#(1::4A$$&

#(1:>:A)$#(1:>1-($!$$#$%*%!:(:?

(45)

:(:D$$$!$#1::J?:.$*#%+*6$&

1::E-.!:(:D:(>@$$!$#>?:+#(1:>1A)$#(1:>1A ,#(1:>4-!:(>>:(>D+"$PN"&>DD3AO&H#(1::@A 6"&#(1:>2-(/8/.$$&#&'!$.$

%$*$##%("!"

$!%$$$*(*&"%$&$$

$$+$#(1:>4-!$#$

+0",$.1::2-(/$"$!$#%"%$#"=

$###9"$$*$&&+%#(>D4E-(.

#$"$$"#!$$*#$

$"#$*(/#"$&$$&$

*#"$"#!%$!*$$("$*"

#$!#$!$$$#$%+$*"##(1::@A*

6$&1::EA6#(1::4A)$#(1:>1A%#(1:>4A,#(

1:>D-($!#$"$$!$#&."#!"$#

!($#.#$*#!#"&$#$+:>-

!%#!$"$&$*#"$"$&#&+%#(1:>4-(/

""%#$$!#$#$%!#""$$"

$!$;"$ $8//( +#*$P0$>DD?-$$#%

"#$$%$&$$8$$$$(/8//."$&

$;"##%.#2E$&$$8$$$##

$$.$>E8$&$$!$1:$&$$$

#%( $ $ $ $ *# 8 # , 1 +1-.

, ?+>-., E+>-., 3+>-., >:+?-., >1+4-., 1:+>1-, 1E+E-.$

"!8$$(.#$#$!$"*$$$*#

(46)

$ $ "#$( $& K *$"#%

, ?., E., 3., >:., >1., 1:, 1E."$$

!!# &$ $&$$ 8 $ 6#$. $ 0. $ N%.

6#$'7$!6#$#"#$+#"&##(1::>A"#(

1::2A#(1:>:A##(1:>>A$#(1:>1A$#(1:>2A 0*#(1:>@A#(1:>@-(70$&$$K

%#"&##(+1::>-, 4%"$&!$##$%##(+1:>>- , >1. , >D , 1E % "$& 8. $*#%( $##$

&!$$$*!$+J$=$+--%$#$&$&#%#%!$&!

#&($##$$&!$#%"!

!&!'$+7$#(1:::-(/""%."#&.

"$&"!!+CE>2D:48-$0#%$

$$% $ & $*#* $ $ ( $ $

"# ! #$" !% =#$ % " *$

&!$$!#$!!$*%

&%(/.!"*$*$&!$!

"%)2(>(>+)!,!#%/L"4-"(7".

8$333"$#"$&#&"!8.!1?8 144!"$%##(+1:>>-#"&##(+1::>-.$*#%(

"!$!##%$#$&$""%!$&!&$

*$$$$0"#$(G$$#$%$$*$"##*#!%=#$

$$"#+,&#%#(1::DA$#M#(1:>4-(0$

* ! &$ *$$ " $& $$# $$& #

&$+(&$(!-(7K$0"#$*

, 1., 2., @., E., >@., 1:., 13+#"&##(1::>A

(47)

$##(1::DA##(1:>>A##(1:>E-(/$##

$$*&$#$$+(&("#(>DDDA6#(1::4-($

#$ #$* $ $! % * 6$&+1::E-&!:(1E:(E1(*#$$#$%.&$&

!:(:1J:(:@$!$#$!#+6$&#(1:::-!:(:EJ :(>1#!#"+"#(>DDDA6$&#(1::2AS#

#(1::@-($$#$%$""%+8/-$!:(1E

&!:(:>:(>1#$*#%$$."$&#$!#(

!$&$##%#$*#%$$$#%

$#$$.$$"$&$*#"$"#0(

.$#"$&#$*#%$$!""%$&$*#"$

$##&$*!$!$$$!*&$#$&$$.$

$ "## "! " $ "#$$#

!$$$"#$(

/""%+8//-*!$"#! $**$

$$. *# >4> "$9" & $ >E4 & ! % ##$& /8

#%( "$& &$ $ $$#% $ !

$&$$8$$%$#&$*#*$#%$$

"$#!$&!+7$&"2-$$"$!*"$*

*$%&#(+1:>4-("#$&#$&$""%

"#%!9"&!$#%&

"$9"#%$#=$#%$$"$!"###!

# !# +8 ///-( !& "# $ 8 //. &.

$*#*$?:J1::.$$$#%*%$&

$!$#($###"$9"1::B2.!$*

(48)

$#&!$.$$$$#!$*

1:::::##<!#$!$#$$$""%!"!$$2!$(

&. . !! #% " $ $$ $

@::B2$&$$?:(&!.! .!.

$$>?:J@::@::. &$$$

$$1::B2$(7"$&"$$$$

& $*$& & =$ $# ! "$!"# !# +8 ///-

!###&$ %+%/%'6-%)+8/G-.$"!"$&"#$$#!$$$

$%#(0=$$###*$##*##

&.$##(&. ""

=$*$8,(&*$"#%"=$#$*

K$"#+$"#(1:>@-"=$#!!#

$6#$+$#(1:>E-($$%$!$

=$ $ *$ # !#( !$$& & = $

"$!"# *$ 8, !# +8 ///-( !# =$

!&=#""#&$+X:(2-$#

$($!$&""$*#%!$!$&$$!$$&

!$&$$&$!"#(.>4!##%$&(/

$$%$&$$"#!#&"%$$#,G$&+X>::.

C>:-*#+T>::.C>:-&#$#%$+J!#*$&.

C>1-#$+*'$&!#*$&.C4-(+# -$

&$#%$&$$$$#=$$"$!"#8,!#(#

$&$$#%$&=$!#!$&,G9'*#"

+:(:1-( &$&=$&"$#,G

$#%#$&$.'*#"+:(:1-9'*#"+:(:?-.$&#%(

(49)

!$#$&#&$"E23DD4!$&$$8#

, E + D: >4@ 3?: . 8 //-. *$"#% $$$ $#" $ "

$#!!% %74)75 "$& #$$# "#$$# !$$ +0$ #(

1::4-(#$"$#'$!$.$*#*$!$*$#"="$#

$ $" +$ #( 1:>@-( "$# #% ! # $ !!!% &#

$!!"$%+G#(1:>?-("$#&$!&."#$####

%$$&#$"$#$$$!!"%!("$&*$

!$$"!"$#!&$$*$!$#."&!$&$

!#!!!!%&#$&$*$&&&$M +*$',%#(1::3-(,!&"$#!&%$

$$#"$*#%$9"$$!!"

+#&#(1::D-($#$%!9"$$!!"$

"$$#$%$$$(/*$!$$$"*$*$$

##&%$%$&&$&#$*$*$!&+

#(1:>:-($!%#$$#!!$+8!1:>?-$$&$!$#

#& $ $!( . $ 0 $ % #

$!%"$&##"#=$#($!$&"#$!

$*$#"="$#$!!"##!#$$"$

&$$*$&&.9"$#%$##!$%$(7".

&$$$*$"#%$$$$ %74)75$$

$ 0 +' #( 1:>2-( $ & #% !$ # $ #$$.

$$$"*$*###+,!$#51:>E-$*

$$!$"$!"#$+6#%#(1:>2-("$#9"$$!%

=#$ # $ !$# $ $& ,G ( / )2(>(> &!

!#% "$", >:+4E443-!>!

(50)

$&$$ 8 $$ +43 D?4 -( " "# ! $$$ & $$&

$ &"#$ $ $ 0 $ !$ " $*$&$(

$$##%. * ! # %!% #% +8 ///- $*$&

#"%"$8,!#$$%"!%##$#

"$$#&=$(6*.$&$$$$#%!%

##"&"$&#,G&#$.$((

"## &!""%$&##"#=$(

"$ * #% *$ & =$ $ !# $!"# $ $

$+)+%#(1:>?A6#(1:>3A0%#(1:>4-(/""%#"$

$$$!!"$#!$#+CE-$&+CE- ,G##&-18-642$ %+%/%'6-%)$>1>:2+8/G-(

$$##%.&"%%.$&+C2-#+CD-$!$#(

$$%&!0 $#!9"!&$

*$&!!#%)2(>(##$&#%$*#?D2EE@@2

$&$$#% & +'*#" T :(:?- $ ##& % >:2 >1

$*#%.*"##&#($#>1>:2.?44&

$$$($$&#,G$#

!#(!%$/7+$-&"'&"#$#,G!#

##& $ >:2 $%# &$$ $!$ @ + - '&"# $ # ,G!###&$>1(&$.$!#$

"$#$$&"$&$#!!$."&"$#!$&$+#*!#(

1:>4- #$"$#&"#$+"M"$#(1::2-(/$&"#

"$&"%$!$#(/"$!"##&"

& #$$ > +- !& $ ##&"

""+-"'&"#$!#$$&(&*

(51)

#$"$!!"###'$#!!%%$$$#

$$. $# & $ $! %#%$ " #$$ !

=##"#(*.&"'&"#$!#$!"#$

>1>:2$$$&!#(6.&$

"&&"$#$!$$!$$.$$$

$&"$!&#&="+8/G-(

$&!%$$$$!#$$*$!$$(

/$$&0$#,G!$&*""$#"

'&"#$ $&$!$#""'&"#$(

"!!$. *# & * $$$ $ $$ $ #$*#% $

$$$0$%($&$##%$!.

$"#%"$"$&$*#"$"#0#.$(($

#%$""%$##*#"#$!$$$!*"#(

# 1:: ::: ##<!# +1::- !!#% " $ * 9"##% $&$$ & >?: ::: ##<!# +>?:-. $$$& $!$# &"

!$!#(7"."#&=$+#.$

-$#"$#$*#!$.$#&

" $ $$ $ 1::B2 $( 6*. " $*$&$

$&$%$!*"$&$"$$#$$

$0#("#%"$!"####$#%$!#!

"$&!$#$.$$$##*#( #%&

=$$#"$&$&#*#."#"$$.!$&""#

"$&"$$&$*#!$

$*$!$#(

(52)

)/

$ $ *$ #& &$ "$# &" $

"#$$#!$$$&$0#"#$(

*##$*$$*$#%($

$#&$#$$!$#%$#!:(:3:(2@

*%$&!:(44:(DD+8/-(

$%'$=$&$$8*#!&$$+8//-(

/$# 8 $$$ >?: 1:: 1?:

2::($$$#%$8.!$&

!#=$%$$(

# $ $& ##"# =$ $ $& ,G

*#$& &$$#"$&%$&$$8 +8//.///-( &*#$&$$&"%

#$&$$&=$$#%$#$(

$&+8///./G-#$&"#$"$#$$&+#.

$ - "$! !"# ## '$#!!%

%$"$$$#$$+-*$$$(

""#$$$$&,G*$#9"$

!$*$!!"%##$&!"$###!#$

&$*$&"(

(53)

808//707))0)/

7"#%$$$$&#. $.

$""$&$$$$$

$0(

*#"$"#$=0$#"$&*#$$

$$!#!$$$$!$&!$!$*(

=$*$&$$$&$&"$$*$"#$

$&#,G"#$"$$$$&(

=$#%$&"!0$$%&$$##%

=&"(

#%#!$#!#!$$*$"##&$$!

+"&"#$$-$"%&*$!$&=$

$#(

(54)

070

>( "#.;((.(0$. (/.((*"$(1::3( ,L0#$%

&!'$ $$ #%$( ,$$!$ 12+>:-L>1D@'>1DE( $L L<<$(&<>:(>:D2<$$!$<!>:4

1( *$.(.N(S(.,(8(%.((#%.0(,.($.(N(#$. ( .,(#!(1:>2(6"!%!&#*$"$#"$'>:#$M

!%$*1%$!!"(N G$#43+>4-L>:132'>:141($LL<<$(&<>:(>>14<NG/(::D>1'>2

2(,!$.(7(#(1:>E(&"#$$$!!$'#%(

*,$#0&"#E1L23'@D($LL<<$(&<>:(>:>E<($(1:>E(:?(::>

@(,. (0(. ( .(8(,#. (8(,$.(,.(""#. ("$.

((7&"'!$.(0($&.(6%.(0(6$&&.( ($.(8(

8$&( 1:>@( $$ $*$&$& #0 "$ $ *$*( #$

2L:2:?4($LL<<$(&<>:(3??@<$(:2:?4

?(,%#.((.( (.(($".((7=.( (,.(0("!#(

>DD4(/##"#%#"""!$"$

$$#$###(//!!"EE+>-L22E'2@1(

E(,&#%.(.7(,"#%.((8$. ((7%.,( (##(1::D($$

"#$!!"$6#$'7$$.&$0.

$ $ #$( N $% $ D1+1-L3@D'3?3( $L L<<$(&<>:(2>E4<(1::4'>2?E

3(,.(.(8.0(7$$.(G$$.((1:>4( #$*

!$##"$=#$#$&$#$!$$$$/#$

(55)

6#$( N $% $ >:>+>>-L>:::>'>::>:( $LL<<$(&<>:(2>E4<(1:>4'

>@413

4(,.(.(0*&#$.(8.(G$$.0(7$$.((1:>D(

$ #$$ #$* !$ ## " $ $ !$# %$#.

!$$"%$$/#$N%( $!$ND:+3-L4:4'4>3($L L<<$(&<>:(>>>><(>21:@

D(,&$.(.($.(0$.N($". ($.(0$.(&.(

7$.("Z.(7$&$(1:>>(&$!$$L"

##$& *$ !$$ &( $ &$ !$$# &L

!!"$$&"#&$#*L@42'@D@(

>:(%.((.((.((#.(&#".N( (,.(($##$.(

((8.(!#%.(6!.( (&.((6"&(1:>?( #%$

*$ !%'$* !& %$"! *$"!

"$""#$$$"$&0 '9(7$$/!!"#&%E($L L<<$(&< 012>:(224D<$!!"(1:>?(:::12

>>(%.((.((G$.0((8(>D4E(!$##"$$

*%$&!$##"$$$$#$#$(N$%$

ED+1-L??1'???($LL<<$(&<>:(2>E4<(::11':2:1+4E-4:@23'@

>1(.8((0($&#(1::@( !%#$(N#$#11+11-L@E21'

@E@1($LL<<$(&<>:(>1::<N(1::@(:3(>?>

>2(6.;(.("#.N(#.N(N($$&.(N&(1::4( #$*

!$ ## " $ !$$ $$ &$ #$( N $% $ D>+E-L1?:>'1?>>($LL<<$(&<>:(2>E4<(1::3':@?D

>@(*#$.,((0$(>DD?( !$#$&$9"$#$$"!!"$'

#!$&(!$1D+1-L2>>'211($LL<<$(&<>:(>::E<&(>DD?(D::2

(56)

>?($=.N(0(.(#*.7(;". ($!.;($.;(.(6".N(($".,(0(

1:>1(#&$#!$$!!!#$&!$$$%#%$!$

$$("@4?+32D4-L23E'24:($LL<<$(&<>:(>:24<">>:41

>E(7$.7(.($.N(N( M.8(,M$.(!$.,($.($!.7(

9.(".($.(M.8($!.8(G!*.(&.

(&(1:::(=$*&!'$#$&$9"$#$$"!$#(!

0>:+1-L11:'113($LL<<$(&<>:(>>:><&(>:(1(11:

>3(##"$.(8(M$&(1::>(&$&#L$!!"%!("

$$$$!!"#&%>2+>-L>>@'>>D(

>4($#.(>D41(% #%$#(N"# $!#$

?@+?-L>:3D'>:DE(

>D(.((.,(N(6%.(6(("$(1:>>()$&&!$#$$

!$=$"%&!$#$(N"# $!#,$&

$>14+E-L@:D'@1>($LL<<$(&<>:(>>>><(>@2D':244(1:>>(::DE@(=

1:(.(7(($M(1:>:( #$*$*$!&L!$!

"$( /!!"$% 21+?-L?D2'E:@( $L L<<$(&<>:(>:>E<($!!"$(1:>:(:?(::3

1>( 6&!'$#. (. )( !"#. ,( ,&#". ( &( 1::D(

0#$$!$##"!$#%$#$$&#$(

N$%$D1+3-L2>1@'2>22($LL<<$(&<>:(2>E4<(1::4'>3>D

11(6!$M.(.(($.(#%.8(.(((1:>3(

& 0*% ! " $ /#!!$( " 0*

8%$#3DL?E3'?D1($LL<<$(&<>:(>>@E<"*'%$#':11?>E':2@2@4

(57)

12(6.,(.6((&.($(1::D(0$"!"#$#$&$

$!$!$##$#!(8?+@-L>:::@?E(

$LL<<$(&<>:(>23><"#(&(>:::@?E

1@(6!.0(N(>DD@(%!$"!'$$$*#"$!$'##"

'8%$#&%$$7 $&!$'##"(N"#$%

$33+3-L1>:2'1>>1($LL<<$(&</>:(2>E4<(::11':2:1+D@-33>?2' 4

1?(6"&.(.,(6$&. (($(1:>2($$$!$

##&'$$"#$$#!$$$&$0(N"#

$!#,$&$>2:+1-LD4'>:?($LL<<$(&<>:(>>>><&(>1:>D 1E( 6#%. (. 8( . N( 0( *$( 1:>2( /!!$ #% & ##

!$( 8!# >23+>-LE@'33( $L L<<$(&<>:(>:>E<(!(1:>1(:D(::>

13(6$&.,(.(#!#.N(0"(>DDD(#$$#!$$$&$#L 9"%.*$!.&$#$$$%$#(N$%$

41+E-L>21?'>22:($LL<<$(&<>:(2>E4<(::11':2:1+DD-3?2?E'3

14(6$&.,(.(#!#.N(0"(1:::(#$!$$$$$%

#L*$$"$"$$$"$($*8"$

$E@+1'2-LD?'>:E($LL<<$(&<$>:(>:>E<:2:>'E11E+DD-::>14'>

1D(6$&.,(.0(0%.($#.(#!#.( ($&#(1::2(,$*$

#%$#$$#$%#$$#!$$"##$&$$'#$(N$%$

4E+1-LE?2'EE:($LL<<$(&<>:(2>E4<(::11':2:1+:2-32E@2'>

2:(6.6((.(( %. ((,(0%.(F((6"%.($.6(N(.N((.

($!(1:>3($!"#"0 '9$$#$#$&$##"#

(58)

,"## " ,( "'$ !"$ !&( $ 8&$

>>2L?3'E3($LL<<$(&<>:(>:>E<(!$(1:>3(>:(:1D

2>(N5&.6(N(. (,(&.(*$#.0((S.(#*.,(*$#.(

( 1:>E( " &#$ $ *$! *$ $% ''

$$& =[ G $$# >4@LE@'31( $L L<<$(&<>:(>:>E<(*!$(1:>?(>1(:>@

21( #"&#. 6(. ( %. ,( 6$&. 6( ( #. ( !M'0%. ( /( G&. /(

#.N(&.(#!#.("#!.N(G$#$.N(0".( #.(

0$&. ( $( 1::>( K"$$* $ #$ $& #$$# !$$

!$##"$$%#(!!!>1+>>-L423'4@1(

22(. (.,(6$&.(&&'.(7".8($.,(7"'##(1:>:(

$#%$#$$#!$$!$##"$$ "$7#*$

(N$%$D2+>1-L?D43'?DD?($LL<<$(&<>:(2>E4<(1:>:'2@?>

2@(. (.7($&#$.(7(#.7((#(1:>1( #$*!$##

"$$!*!$$$$$6#$(N$%$D?+>-L@21'

@2D($LL<<$(&<>:(2>E4<(1:>>'@32>

2?($*"#.(.(&"$.( (%$(1::@($!'%

!$ ## " $ #$ & 7$$ $% #( $*

8"$ $ D:+1'2-L>@?'>?3( $L L<<$(&<>:(>:>E<(#$*$(1::@(:2(::@

2E( $&.N(. ( ( '*. N( /'#!(1:>4(*#"$%$#$%

#&$##%$$&!$$$$*&&"#$(, ,$#>E+>-L43($LL<<$(&<>:(>>4E<>1D>?':>4':??E'=

23(".(.N(,$M.(0$.(F".6(!.(.( (,!.(

$. ( $!. ( 6$#. ( . /( "&. ( 7. ,(

(59)

,$&.7(0$.0(0./(0".( *".N(,#"!#.(#!(1::2(

K"$$* $ #$ !$& "$# $ $ ! 6#$ #

"#$(N$%$4E+>-L2E:'2E4(

24( . (. ( ". 0( $( 1:>E( # $$&L 6 6$

$$$ 0&"# =$( 21+>-L@1'?E( $L L<<$(&<>:(>:>E<($&(1:>?(>:(::3

2D('. ((.((,!. ($&.0(#. ((./(

#(1:>2(#%$!*$!%'$*!&

$ $ %#" "" $ *$( , !$ >@L4D>( $L L<<$(&<>:(>>4E<>@3>'1>E@'>@'4D>

@:('. ((.N(".6((%./(#(1:>1(!$$&

9"$$* $ #$ &" !$% #% *# "$*

$ % $& !$$ $ #( $! @2+E-L3D2'3DD( $L L<<$(&<>:(>>>><(>2E?'1:?1(1:>1(:12@1(=

@>($.,(1:::(G//(=)$*$%8/(.;(

@1($".;(.6(&.(&.,(N$&.(S(1:>@(=$#%$#$>

#$1$$$"!"#'$*##K$"#(#0

>2+@-L43E3'433?($LL<<$(&<>:(@124<1:>@((13(>4

@2( & Q( 1::D( /"## "*% " &!$ $!$( /"##

,"##$2D(

@@(*.(/(.(6".( (1:>@($!$#&

$$ 0 '9 $ 91( ! ,$# >?+>1-L??:( $L L<<$(&<>:(>>4E<>2:?D':>@':??:'4

@?(".((.N(N.8(6(8(>DDD($!$&$%$

!#$$#!$$.!$##"$*$.$%$#$

(60)

$% # "$& $ !#$&( N $% $ 41+?-L>:@?'>:?>( $L L<<$(&<>:(2>E4<(::11':2:1+DD-3?21?'3

@E("$. (N(N"&(>DD3($0#$$$#;$#.!$##

".$$.$#$#$%&$7$$$%#8"#$(/"##

,"##$+>?-L(34'42(

@3(.8(1:>1(!"( &!=$&$&"$!#

!#&$&(G$1( ")$*$%(

@4( . 8( N( N( 1:>2( )W "$ )( 8& #%$&

"#$*$$=#(G$E.#?(1( ")$*$%(

@D($.8(.6((,!.(7(,$.((%.7($&#$(1:>4(%!$"!

*$L *# &$ &$##% $!* !$$ $ $ $% #( N

$%$>:>+2-L131@'132E($LL<<$(&<>:(2>E4<(1:>3'>2??@

?:(""!##$.((.((#%.0((#.N(7(%#.(7( ##.(8(6.

N(\##.((.(8(!$.((&.(8(G##(1::D(

*#!$M$$&$%8&%$&%#(

8@+@-L?2?:($LL<<$(&<>:(>23><"#((:::?2?:

?>($.,((.(8(,%.7(%.((7$#%. ((7%.((,#%.(

N( %( 1:>2( &!'$ $$ "% !$ ## "$&

/##"!$$&'$%*$$$$$*#*#K$##%#

!$$ "$$#$%( 7 @L11D( $L L<<$(&<>:(224D<&(1:>2(::11D

?1($.,((.7(N(%.((7$#%.((,#%. ((7%.(8(,%.

(N(%(1:>1(!'$$$!$#"$!$##

$ 6#$'7$$ # $ /#( , >2L1>( $L L<<$(&<>:(>>4E<>@3>'1>?E'>2'1>

(61)

?2("$.(6(.,(N(6%.(((1::>(8$$#&$*#"

"$&&!'$!!($>?3+@-L>4>D'>41D(

?@($#M.(.(7MM.($#MM$.N(($##$!.N(M%(1:>4(

%"!*$$$,""L$$*$"#'$'*$$#$%(,

!$>D+>-L@>:($LL<<$(&<>:(>>4E<>14E@':>4'@4>?'E

??($##.0(6(.(N(8.( (7"#(>DD>(G$$$!$#!$##$

$#*$&(N$%$3@+>>-L2341'23D:($LL<<$(&<>:(2>E4<(::11' :2:1+D>-34?3:'E

?E($.(.N(,(&.((S.6($.;((S&.(($.6(N(;&.(S&.

N(K(&(1:>E(8#!'!$*#$!!".!#!

&"#$%$$'#$&$%(N"#

8!$>@ELDD'>:4($LL<<$(&<>:(>:>E<((1:>E(:E(::4

?3( #. (. ( 0!". ( ( 8%. ( /. ( "$( 1:>:(

$M$0 !$(!01:+3-L4DD'D:3($L L<<$(&<>:(>>:><&(>:2@32(>:D

?4( . 0(. ( 8$. ( %. ( ##( 1:>1( N$ $!$ &$

!'%!$##"!$$$)$$&!(N$%

$D?+4-L@E>4'@E14($LL<<$(&<>:(2>E4<(1:>>'@D3>

?D(%.((.7($&#$.( (9*$.7(#$$.8($.6((,!(

1:>4($#%$"#$$#!$$$#%#$$"$&

#$ # !#( N $% $ >:>+>1-L>>>1:'>>>2>( $L L<<$(&<>:(2>E4<(1:>4'>?>1E

E:($#.6(.6((#.,(6%.(!.(.(*.(6("$.

( $( 1::D( $M$ K &$ $& #$$# !$$

(62)

$%$#, E( $!@:+?-L3:>'3>1($LL<<$(&<>:(>>>><(>2E?' 1:?1(1::D(:>D:4(=

E>(\,$.N(.6(6%.;(S%.(8&(1:>4(**$$0 ,$&$.

$! $. $"#$( 7 $# +"- DL@:1( $L L<<$(&<>:(224D<(1:>4(::@:1

E1(#.6((.((". (('.6(*.(!.(*.

( %$.(#.((".(0(#.,(6$&.6(6(6.

/( #. ( 8( . ( $( 1:>E( 7$ !$& K *$

!! E "$& $!" "## 9" "&& % # &"'

$$!+-&$#$$#!$$!$#"$(#*#

@4+>-L3D($LL<<$(&<>:(>>4E<>13>>':>E':1?3'1

E2(#.((.(8(".0((#!.N((7.N((#.N((".8($!.N(

,( . ( ( #$. N( ( S( 1:>?( , $ *#"$& $&#

"#$ *$ ##$& ! !$$# &!$( 7 EL12?( $L L<<$(&<>:(224D<&(1:>?(::12?

E@(*$',%.N(.N(N(G#M' #.('N"M. ('SM.N((M' M. (,*'8$.G((,$M#' &"$(1::3(/$!!"

*$ !!!% &# &$ $ $# !$$( N /

?@+@-L2DD'@:D($LL<<$(&<>:(>:>E<($(1::E(:E(:>:

E?(8.N((.(6"##.8((0"&&(1::D(%!$!$##"

$!!!% $$ % $( 8* G D:+>'1-L@2'?@( $L L<<$(&<>:(>:>E<(*!(1::D(:2(:>1

EE(8!.8(1:>?($!!"%!(#$.%#P7$".(

(63)

E3(8$#.0(.(0!!$.N(,($(1:>2(0#$#$$$$&!$*$

! 0 '9 ( ! N 6"! D2+@-LE@>'E?>( $L L<<$(&<>:(>:>E<(&(1:>2(:4(::4

E4(8.,((.(0%.G($#.7(;".(".(.((G.;(&.0((

6. ( ( $#. 0( ( "!. ;( &. ( "#%. N( 6( $. ( 8(

%.N( (!%"#.N(%#.0((6$.(*$.,(0.

(($#(1:>@(#&$##%$$&!$#"$#$$'

$!$&&"#$("?>?+3?13-L@:1'@:?($LL<<$(&<>:(>:24<">2D4E ED(0$.8(.(7".(,$.0(0"(1:>4(/*$*$L!$#!$

## " "$$#$% !$$( N $% $ >:>+4-LE3:2'E3>@( $L L<<$(&<>:(2>E4<(1:>4'>@?D2

3:( 0$. 8(. ( 7!&". 8( ". 7( ,( $#( 1::4( %#" ""

#$$$ $ $&& $#!!$ $ #$& *$ !!!% &#(

G$%02D+?-L?1($LL<<$(&<>:(>:?><*L1::4:2@

3>(0.((8(.(6(6"#%.((".((!*./((,*.N((0$.

((./(#. ((!.((.(( $(1:>@( 2 6"! ! $# 0#"$ 0*# 8$$# !$

$&(##>?D+3-L>EE?'>E4:($LL<<$(&<>:(>:>E<(##(1:>@(>>(:1>

31(0*.( (.,((.,(N(6%(1:>@("#$&!$$$

$!*$$!$&"$**$"#%$&!$#"$$$%

#(,!$>?LE1($LL<<$(&<>:(>>4E<>@3>'1>E@'>?'E1

32(0$.(( (#(1:>:( #$&!#$M$!$$#

=$ #%$ 0 '9 ( ! ,$# >>+2-L01?( $L L<<$(&<>:(>>4E<&'1:>:'>>'2'1?

(64)

3@(0%.(.(!$.,(M$.( .( #!.(M".(!&".(8(

8$.6($.(/.(!.8($$.;(6%$M$. (0(0(7.

0("#.G(,(,$.7(,!.6("M"$(1:>4($$##

%$"! ""#$ $$ $ !&( $$$ 0 4( $L L<<$(&<>:(>:24<@>?D4':>4'1@?:D'E

3?(0".(G(.(,$&.(6.(.((!. (%.(6"(

1:>?( !$* 6$' 0*# 7 )#$ *#"$ !!#

!$ $"( ## 0 >:+4-L>1D3'>2:D( $L L<<$(&<>:(>:>E<(#(1:>?(:1(::@

3E(0".0((,$(1::2($$!$$$$%#(G0 2@+?-LE3>'E44($LL<<$(&<>:(>:?><*L1::2:1:

33( . (. ,( "#. ( ,$=. ( ( "( 1:>:( !'$

$$!$&!#$#$%$$$$6#$#(

$!@>+E-L?3D'?44($LL<<$(&<>:(>>>><(>2E?'1:?1(1:>:(:1:E@(=

34( . (. ,( "#. ,( !. ( ( 6#!. 7( 8$M. 0( 7( ,"!. ( ,$=.(("(1:>@(!'$$$"%"$&$&'$%

$&# "#$ #%!$! % #'&! 9" #$$#

!$$ $ $ $% #( N $% $ D3+>>-L31?4'313?( $L L<<$(&<>:(2>E4<(1:>@'4>@>

3D(.(.,("#.,(!.(("(1:>2($!$$'

!$& #$$# !$$ !$ ## K $ $ 6#$ #(

$!#$@@+E-LE1:'E1E($LL<<$(&<>:(>>>><&(>1:?2

4:(#*!.(.0(8$.((. (S.8(.(#.($.

(#$.,(#M&(1:>4(%$>$$$##%9"$"$#

(65)

!$&$$2*$!"$&"$#!!$(,#>2>+>3-L>443'>4D4(

$LL<<$(&<>:(>>41<#'1:>3'>:'4>>4?>

4>( $%. 6(. ( #!&. 6( 6( %. 0( ( ,"!$( 1::E( "%

"#$!0 =$$#!!%$9"!$#$

$ !$ ## #*# $ $% ( N $% $ 4D+3-L1@3D'1@4E( $L L<<$(&<>:(2>E4<(::11':2:1+:E-31211':

41(. (N(.(N(!.;(6(".N(,($#!$.(N(6!(>DD3(

$!$*$!!$##"!$#

"$ 9"( N $% $ 4:+4-L>422'>4@:( $L L<<$(&<>:(2>E4<(::11':2:1+D3-3E>>4'E

42(".;(6(.((#$. (N($.(($(>DD1($,"#$#

!$'## " 0"$ 8&! (1( %!$ ,"# $# !$'##

"( N $% $ 3?+>1-L22?D'22EE( $LL<<$(&</>:(2>E4<(::11' :2:1+D1-34>>1':

4@( M. (. )( ( $. ( $&. ( ,"&!. ( #M. ( S. (

#.(8(M%(1:>>($$$$###"$!$#

*#"$ $#!!% $ $ #$$##% #% "#$$##% $

*$ !!!% &#( N $% 0 34+@-L@@4'@??( $L L<<$(&<>:(>:>3<::11:1DD>>:::?3@

4?($. (.(#$&.(("!#.N($#.8(0$.;("(1:>@(

/!$!!!%!&=$$#$*$$$

#$!$$(8D+>-L4??3D($LL<<$(&<>:(>23><"#((::4??3D 4E( !$. ,( 8( 1:>@( & $!# /# $$( #*$ 6# $. @

$$L>:>?'>:@2(

(66)

43(#.(.(8(.6((#.( (#.(*.(.,(N(6%.

($(1:>>(K"$$*$#$#$$#!$$!!1.E.>@

1: $ &$ 0 #( $! @1+?-L@?3'@E?( $L L<<$(&<>:(>>>><(>2E?'1:?1(1:>:(:1>E?(=

44(#&.(.(.,(6$&. (6&$.((#(1::D(/!!"

! *$ #"! !$#( N $! $ 43+>2 "#-L2'D( $L L<<$(&<>:(1?13<(1::4'>233

4D("M"$. (.0(;!.F(&.("$.(.("M"$.(&$.(

%!'6!.0($.(.("$.6(7"".(;$.(

;"$.(!.(".($$.0($!.;($$. ($. ( /$. ($.(".;(!".(;!!(1::2(7"$#

#%8 /@.$&$"##$$&M%!$%#&$$$!$@.

$ $ "!$ $$( 2@+@-L2D?'@:1( $L L<<$(&<>:(>:24<&>1:E

D:(*.(,(6$&(1::E(!$##"$$"'#$$#

!$$($!#$$#$$#!$$(/"##,"##$

+2?-L>1(

D>( *$*. ( 0(. ( /( =*$. ( ( ,#&*. ( ( * "$. ;( ( "#( 1:>1( 0$ *$ !' ! #'&!

$$ #%$( " $ @@+>:-L>>EE'>>3:( $L L<<$(&<>:(>:24<&(1@>:

D1()$.N(/(.N(7M.N(N($$&.(&(1:>1($#$$!&

!$$ #$* !$ ## " $ $ $ 2 #$ $ 6#$(N$%$D?+E-L2@14'2@2@($LL<<$(&<>:(2>E4<(1:>>'@32D

(67)

D2(G0.8((1::4($$!!"&!$$$(N$%$

D>+>>-L@@>@'@@12($LL<<$(&<>:(2>E4<(1::3':D4:

D@(G0.8(((0($&&(>DD>($*$.#"#$."$#

$!# !# $!$( N $% $ 3@+4-L1323'13@E( $L L<<$(&<>:(2>E4<(::11':2:1+D>-34@?2'>

D?(G.N(.(8$.(8$.(G8".(8#!. (G$.(

G#$&(1:>?(!$##"!$#"$#*$$#$%$%$$

$$ F0> &% ##$& =$!# $!!!% $$ $

%#" !& $&$$& ! !$#( G N 1:@+2-L211'21E( $L L<<$(&<>:(>:>E<(*#(1:>?(:@(:>:

DE( G$. G(. 0( S( !. ( !#( 1:>D( " !"#$#

!$$#%$!#$M#"#$!$##$#

$ !"#$# $!% "!( , 0 # >D+>-L>1D( $L L<<$(&<>:(>>4E<>143@':>D':3?@'@

D3( G$&"$. (. ( . ( $#!$. ( #. 0( \%( 1::D( $$

$L"""$*(,$#13+4-L@4E'@D2($L L<<$(&<>:(>:>E<($(1::D(:?(::@

D4(&.(.(8(6. (N(!#$.(N(GN&.N((8%.,((.

((.,(N(6%(1:>4(8"$**$#&$#$$!$

7$$&!$""$*&"#%*$

!#=$(,!$>D+>-L2D?($LL<<$(&<>:(>>4E<>14E@':>4'

@4::':

DD(.N((.( (,.(8(,##. (.(*$.0($(1::4(#"#

$#&%&(8"$/(."#$$&,!$"!!$&.

7$(

(68)

>::($$&.N(N(.("#.N(#.(N&.0(7(G!.;(6(

1:>:(!$$&!$##"$$!##$&$!$$(N$%

$D2+@-L>ED:'>3:>($LL<<$(&<>:(2>E4<(1::D'1:?1

>:>(".F(.((".(.,("#.(".K(S&.("(1:>?(

$$#%$"#8'#9"$$

6#$(#*#@3L?:($LL<<$(&<>:(>>4E<>13>>':>?':>1D'>

>:1(;.N(.("#"$./(S%./("".(0M.(((1:>1(

8$!', L#$&&'$$$!#%!$$(

,,$$!$>2L>2@($LL<<$(&<>:(>>4E<>@3>'1>:?'>2'>2@

>:2(S.0((.(,(*".(.((7=.6((,!.;(6(".

(*,#"!(1::1(!$%#"""$#!*$

"!$.!$#$&9"$!.*$!$#%&%$&."#'$#&#

#$.$%%$&(N#$$$#@:+>>-L24D@'2D:1(

>:@(S#.(0(.( ($&#.;((&.0((#.N((#%(1::@($

#$#$"$&"'(/(/$.$$#$%

$!. $ $& *#"( N $% $ 43+>1-L@143'@1D@( $L L<<$(&<>:(2>E4<(::11':2:1+:@-32?32':

>:?( O&. N(. ,( 6$&. ( #!#( 1::@( !!"$$L $*$

&$#%$#$$#!$$!$##"$&$$%#(

N"# $% $ 43+>:-L2?>?'2?>3( $LL<<$(&<>:(2>E4<(::11' :2:1+:@-32@43'E

(69)

(70)

(71)

(72)

(73)

!" "

Chronic subclinical mastitis (SCM), characterized by changes in milk composition and high somatic cell count (SCC) in milk for a prolonged period of time, is often caused by a bacterial infection. Different levels of SCC have been suggested and used as threshold to identify subclinical infection. The aim of this study was to examine different definitions of SCM based on test-day SCC and estimate genetic parameters for these traits and their genetic correlation to milk production.

Test-day SCC records from 1,209,128 Norwegian Red cows in lactation 1 to 3 were analyzed. Twelve SCM traits were defined as binary with 2 test-day SCC in a row above SCC thresholds from 50,000 to 400,000 cells/

mL (SCM50, SCM100, SCM150, SCM200, SCM250, SCM300, SCM350, and SCM400), with 3 test-day SCC in a row above 200,000 and 400,000 cells/mL (SCM200_3 and SCM400_3), and the number of days before the first case with SCM50 (D50) or SCM400 (D400). The heritability and genetic correlations were estimated for SCM traits and the mean lactation- average somatic cell score (LSCS) using linear animal repeatability models. The total mean frequency of SCM ranged from 1.2% to 51.8%, for different trait defini- tions, high for low SCC threshold (SCM50) and low for the highest SCC threshold (SCM400_3). For the 2 traits based on number of days, the mean values were 104 (D50) and 117 (D400) days. The mean LSCS was 4.4 (equivalent to around 82,000 SCC). Heritabilities for the 12 alternative SCM traits were low and varied from 0.01 (SCM400_3) to 0.1 (SCM100), whereas for LSCS the estimated heritability was 0.3 and standard error varied from 0.001 to 0.003. Genetic correlations among the SCM traits ranged from 0.7 (D50 and SCM400) to 1 (SCM350 and SCM400), whereas between SCM traits and milk production the correlation ranged from 0.07 (LSCS) to 0.3 (D400). The standard error for genetic

correlations varied from 0.001 to 0.06. The heritability was low and the genetic correlations were strong among SCM traits. Genetic correlations lower than 1 suggest that the alternative SCM traits are genetically different from LSCS, the trait currently used in genetic evalua- tions for Norwegian Red. Hence, the alternative traits will add information and improve breeding for better udder health.

Key words: somatic cell count, Norwegian Red, heritability, genetic correlation

" #"

Mastitis is one of the most frequent and costly dis- eases in dairy cattle, characterized as an inflammatory process in the mammary gland, often with increased SCC in milk (Harmon, 1994). Clinical mastitis (CM) is characterized by clinical symptoms such as severe udder inflammation, whereas chronic subclinical mas- titis (SCM) is recognized by changes in milk composi- tion such as high SCC for prolonged periods of time (Harmon, 1994; Østerås et al., 2007). Normal SCC in healthy udder quarters has been reported to be lower than 100,000 cells/mL (Schwarz et al., 2011). High SCC, commonly used to characterize SCM, is defined as more than 200,000 cells/mL, and will often lead to decreased milk production (Dohoo and Leslie, 1991;

Harmon, 1994; Schepers et al., 1997; Østerås et al., 2007; Pantoja et al., 2009). Staphylococcus aureus and Streptococcus agalactiae are known as some of the most common bacteria causing udder inflammation. Ac- cording to the health status report for Norwegian Red (NR) cows in 2017, S. aureus is the major causative bacterium of mastitis, found to be present in 25.4% of milk samples (TINE SA, 2017). Somatic cells consist of epithelial cells together with polymorphonuclear leu- cocytes and macrophages involved in defense against infections in the udder (Miller et al., 1991; Schwarz et al., 2011). Hence, the amount of these cells in milk gives an indicator of the inflammatory process in the udder.

Alternative definitions of the SCC-based mastitis traits have been analyzed previously. Windig et al.

07)52%7-9)68&'0-2-'%01%67-7-675%-76*35+)2)7-')9%08%7-32-2(%-5;'%770)

-56%239%)5-2+67%( ):%2(3:6/%!%&%7%2(06%/)5

-6)8:3-4:5.)91+$+1-4+-9)4,7;):1+-,1+14-)+;2:>5.'-:-814)8>-,1+14- 58=-/1)4&41<-891:>5.1.-$+1-4+-9 ! !925 58=)>

-6)8:3-4:5.413)2)4,7;)+;2:;8)2$+1-4+-9)+;2:>5.159+1-4+-9 58=-/1)4&41<-891:>5.1.-$+1-4+-9 ! ?9 58=)>

-458--,14/)4,995+1):154 ! )3)8 58=)>

%-5;!'- <

,7746(3-35+.(6

A %0-;:0589";*2190-,*>$$4+)4,29-<1-84+54*-0)2.5.:0-3-81+)4)18>$+1-4+-995+1):154@

%01919)456-4)++-99)8:1+2-;4,-8:0-( 21+-49-0::6+8-):1<-+53354958/21+-49-9*>4+4,

Received December 5, 2018.

Accepted February 11, 2019.

*Corresponding author: elena.kirsanova@ nmbu .no

Referanser

RELATERTE DOKUMENTER

The number of genes detected using the UCSC Genome Browser across the defined traits ranged from 11 to 28 and from 4 to 76, based on the human and mouse TAD position respectively..

Figure shows number of differentially expressed genes after pressure treatment for each time point for (a) strain RO15 and (b) strain ScottA. Red bar represents the number

In this study, we examined the expression of selected genes and the miRNA profiles of immature macrophages (primary cells) infected in vitro with the ST103 or ST12 strain

The CXCL1 gene was observed to have a higher level of expression in the group of cows with high GEBV for LSCS, that is, cows with expected low probability to get high SCC level in

The venn diagram above shows the overlap of genes that were differentially expressed (gray numbers) or adaptively differentiated (black numbers) between Atlantic (A) and

We repeated these experiments in primary human monocyte-derived macrophages (HMDM) and observed a similar lack of inflammasome activation when challeng- ing with virus alone but

FIGURE 1 | Venn diagrams of differentially expressed (DE) genes in bovine monocyte-derived macrophages (bMDMs) challenged with Streptococcus agalactiae strain ST103 or strain

Statistical model comparison in genetic analysis of challenge test data on Streptococcus agalactiae resistance in Nile tilapiai.